r-1,t-2-Cyclopropandicarbonsaeuredihydrazid | 2374-08-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: r-1,t-2-Cyclopropandicarbonsaeuredihydrazid
• 英文别名: (1R,2R)-cyclopropane-1,2-dicarbohydrazide
• CAS: 2374-08-5；2722-30-7；41556-36-9；41556-37-0；89365-16-2
• 化学式: C₅H₁₀N₄O₂
• 分子量: 158.16
• InChiKey: SCWLBXZTXMYTLF-PWNYCUMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  r-1,t-2-Cyclopropandicarbonsaeuredihydrazid 在 盐酸 、 sodium nitrite 作用下， 生成 1,2-trans-cyclopropyldiamine
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹²N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines

  摘要：

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

  DOI：

  10.1021/jm980172v
• 作为产物：
  描述：

  反-1,2-环丙烷二羧酸二乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 以80%的产率得到r-1,t-2-Cyclopropandicarbonsaeuredihydrazid
  参考文献：
  名称：

  Conformationally Restricted Analogues of ¹N,¹²N-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines

  摘要：

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.

  DOI：

  10.1021/jm980172v

文献信息

• Saal, Wolfgang von der; Reinhardt, Robert; Seidenspinner, Hubert-Matthias, Liebigs Annalen der Chemie, 1989, p. 703 - 712
  作者：Saal, Wolfgang von der、Reinhardt, Robert、Seidenspinner, Hubert-Matthias、Stawitz, Josef、Quast, Helmut

  DOI：——

  日期：——
• Saal, Wolfgang von der; Reinhardt, Robert; Seidenspinner, Hubert-Matthias, Liebigs Annalen der Chemie, 1994, # 6, p. 569 - 580
  作者：Saal, Wolfgang von der、Reinhardt, Robert、Seidenspinner, Hubert-Matthias、Stawitz, Josef、Quast, Helmut

  DOI：——

  日期：——
• COMANITA E.; TUTOVEANU M.; BOUCHI AL DARBAGH E. A., BUL. INST. POLITEHN. IASI, 1980, SEC. 2, 26, NO 1-2, 17-24
  作者：COMANITA E.、 TUTOVEANU M.、 BOUCHI AL DARBAGH E. A.

  DOI：——

  日期：——
• Conformationally Restricted Analogues of ¹<i>N</i>,¹²<i>N</i>-Bisethylspermine:  Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines
  作者：Venodhar K. Reddy、Aldonia Valasinas、Aparajita Sarkar、Hirak S. Basu、Laurence J. Marton、Benjamin Frydman

  DOI：10.1021/jm980172v

  日期：1998.11.1

  Eight analogues of N-1,N-12-bisethylspermine (BES) with restricted conformations were synthesized in the search for new spermine mimetics with cytotoxic activities. By replacing the central butane segment of BES with a 1,2-disubstituted cyclopropane ring, a pair of cis/trans-isomers was obtained that introduced a spatial constraint in the otherwise freely mobile butane chain. An analogous pair of isomers was obtained when the butane segment was replaced with a 1,2-disubstituted cyclobutane ring or with a 2-butene residue. The six new BES analogues thus obtained.(three pairs of cis/trans-isomers) were growth inhibitory at low-micromolar concentrations against four human tumor cell lines (A549, HT-29, U251MG, and DU145) but were less growth inhibitory against two other human tumor cell lines (PC-3 and MCF7). N-1,N-12-Bisethylspermyne, where the central butane segment of BES was replaced by the rigid 2-butyne segment, was devoid of growth inhibitory activity against five of the six human cell lines studied (DU145 being the only exception), a clear indication of the importance of conformational mobility at the N-4,N-9-butane segment of BES for its biological activity. When the butane segment was replaced by a benzene-1,2-dimethyl residue, the resulting BES analogue was devoid of growth inhibitory activity despite its cisoid conformation. The cytotoxicity of the analogues does not seem to be directly related to their uptake by the cells or to their effects on cellular polyamine levels. BES analogues with restricted conformations but which contained the equivalent of a two-carbon unit, rather than the natural four-carbon unit, at the central segment, such as 1,2-diaminocyclopropyl or 1,2-diaminocyclobutyl derivatives, were devoid of growth inhibitory effects at the concentrations studied. The development of conformationally restricted polyamine analogues appears to show promise in the further quest for polyamine-related therapeutic agents with specificity of action.